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Field of metastatic renal cell cancer (mRCC) treatments is now evolving at a rapid and unprecedented pace. Nivolumab prolongs survival in patients with metastatic kidney cancer with a favorable safety profile as demonstrated in the Check-Mate 025 clinical trial. Nivolumab compared to everolimus prolonged survival in patients with mRCC while exibiting favorbale safety profile. In this study we present the results of nivolumab treatment in patients with mRCC within named patient program (NPP) at UHC Zagreb. In 30% of included patients survival was longer than 30 months and 16.6% patients had a complete response., Područje liječenja metastatskog raka bubrega (mRCC) je područje ubrzanog razvoja terapijskih mogućnosti. Nivolumab produljuje preživljenje bolesnika s metastatskim rakom bubrega uz dobar sigurnosni profil što je pokazano u kliničkoj studiji CheckMate025. Nivolumab u usporedbi s everolimusom produljuje preživljenje kod bolesnika sa mRCC uz povoljni sigurnosni profil lijeka. U ovoj analizi smo prikazali rezultate liječenja bolesnika nivolumabom u NPP u Kliničkom bolničkom centru Zagreb tijekom 2016. do 2018. 30% bolesnika ima preživljenje dulje od 30 mjeseci, a 16.6% je imalo kompletni odgovor na terapiju.

Forty two to 57% of patients with metastatic renal cell carcinoma (mRCC) receive the second-line therapy according to available data. In our analysis we wanted to determine the percentage of patients within intermediate/poor prognostic group mRCC who continued the treatment with the second line following progression on the first line and the percentage of patients who were not able to receive the second line treatment. Patients received sunitinib (first started on 12 August 2018) or pazopanib (first started on May 2014) at University Hospital Center Zagreb. The latest treatment started in December 2018. Our results show that 39.4% of patients who received sunitinib and 37.9% of patients who received pazopanib, did not receive the second line treatment, which is consistent with available data. The question arises whether we could have helped those patients if we had access to newer therapeutic options., Prema literaturnim podacima oko 42% do 57% bolesnika smetastatskim karcinomom bubrega primi drugu liniju liječenja. Retrospektivnom analizom naših podataka htjeli smo prikazati postotak bolesnika s metastatskim karcinomom bubrega koji pripadaju srednjoj/lošoj prognostičkoj skupini a koji su nastavili liječenje drugom linijom nakon progresije na prvolinijsko liječenje. Također smo htjeli prikazati postotak bolesnika koji nisu bili u mogućnosti nastaviti drugolinijsko liječenje. Bolesnici su primali sunitinib (prvi bolesnik je započeo liječenje u svibnju 2014.) i pazopanib (prvi bolesnik je započeo liječenje 12. kolovoza 2018) u Kliničkom bolničkom centru Zagreb. Uključeni su bili bolesnici koji su liječenje započeli do kraja prosinca 2018. godine. 39.4% bolesnika koji su primali sunitinib i 37.9% bolesnika koji su primali pazopanib, nije primilo drugu liniju liječenja, što se podudara s literaturnim podacima. Nameće se pitanje, jesmo li navedenim bolesnicima mogli pomoći da smo imali dostupne novije terapijske opcije.

Objective To conduct a systematic review and meta-analysis of the role of SBRTdrug combination in patients affected by mRCC and associated oncologic outcomes and toxicity profiles. Evidence acquisition We performed a critical review of the Pubmed, Medline, and Embase databases from January 1, 2000 through April 30, 2020 according to the Preferred Reporting Items and Meta-Analyses statement. To assess the overall quality of the literature reviewed, we used a modified Delphi tool. Evidence synthesis A total of 6 studies were included, corresponding to a cohort of 216 patients. Tyrosine Kinases Inhibitors were the most widely used drugs in combination with SBRT, being administered in 93% patients. No study reported an increase of radiation-induced toxicity. Conclusions SBRT resulted to be safe, without increase in terms of drugs-related adverse events in this setting. Moreover, this approach showed promising clinical outcomes in terms of LC and OS

The paper provides the first interim analysis of a database including information on 806 metastatic kidney cancer patients receiving targeted therapy in the cancer facilities of the Moscow Healthcare Department. It shows a comparative analysis of the periods of first-line targeted therapy with different drugs until progression is established.

A 63-year-old male with a past history of left nephrectomy due to clear cell renal cell carcinoma at the age of 57 was admitted for further evaluation. Enhanced abdominal computed tomography revealed that there were several hypervascular tumors in the pancreas and a single hypervascular tumor in the gallbladder. Laparoscopic cholecystectomy was performed to obtainpathological diagnosis. Microscopically, the tumor in the gallbladder was filled with clear cells and was diagnosed as metastatic gallbladder cancer from the previous clear cell renal cell carcinoma. Metastatic renal cell carcinoma to the gallbladder is extremely rare, with reported frequencies of less than0. 6% in687 autopsies. We hereinreport a case inwhich cholecystectomy enabled a successful diagnosis and review the reported 22 cases in Japanese patients.

Xanthogranulomatous pyelonephritis (XP) is an uncommon, chronic, destructive, granulomatous disease of the renal parenchyma. The condition is generally associated with long-term urinary tract obstruction and infection, although the precise etiology of disease remains unknown. The condition often mimics neoplastic and inflammatory diseases, and XP associated with actinomycosis is extremely uncommon. A 60 year-old male was admitted complaining of abdominal pain and weight loss. His radiological findings were suggestive of metastatic kidney cancer, and we performed radical laparoscopic nephrectomy and mesenterectomy for diagnostic purposes. Pathologically, actinomycosis combined with XP was evident. We report here a rare case of XP associated with actinomycosis. (Korean J Med 2016;90:78-82)

The objective: the study of the expediency of the performing of lymphadenectomy (LAE) in the surgical treatment of metastatic kidney cancer (KC). Patients and methods. The study was based on the analysis of the results of treatment of 29 patients with metastatic KC. All the patients undergone LAE. Five years have passed since surgery in all the patients. Results. Metastases in lymph nodes (LN) have been histologically verified in 15 patients. Conclusion. LAE in metastatic KC may have medical significance in case of confirmation of metastasis in a single LN as it provides the same survival rates as in the patients without metastatic LN. Metastases in several LN is a factor of infavourable prognosis at KC.

TPS761 Background: Randomized data from the interferon era demonstrated modest survival benefits of cytoreductive nephrectomy (CN) in patients with advanced renal cell carcinoma (aRCC). Results from SURTIME and CARMENA, conducted in the VEGF-targeted therapy era, have challenged the routine use of upfront CN especially in IMDC intermediate and poor risk patients. Furthermore, the treatment landscape in aRCC now includes first-line combination immunotherapy. Data from the Checkmate-214 trial showed that intermediate/poor risk patients have improved overall survival and objective response rate with ipilimumab and nivolumab (I/N) compared to sunitinib. Stereotactic body radiation therapy (SBRT) provides a convenient method for cytoreduction of the primary kidney lesion and may induce an ‘abscopal effect’, leading to enhanced systemic anti-tumour immune response. We hypothesize that SBRT to the primary kidney mass in aRCC patients will enhance the efficacy of I/N compared to standard of care I/N alone. Methods: This phase II trial randomizes untreated aRCC patients in a 2:1 fashion to I/N plus SBRT (30-40 Gy in 5 fractions) to the primary kidney mass between cycles 1 and 2 (experimental arm, E), versus standard of care I/N alone (standard arm, S). Eligible patients have biopsy-proven aRCC (any histology), IMDC intermediate/poor risk disease, and who decline or are unsuitable for CN. Patients with a primary kidney lesion ≥ 20cm, previous abdominal radiation precluding SBRT, or who have a contraindication to I/N are excluded. The primary objective is to compare the efficacy of I/N plus SBRT versus I/N alone, as determined by the hazard ratio for progression free survival (PFS). Secondary objectives include evaluation of safety, overall survival, objective response rate, and health-related quality of life. Exploratory analyses include blood immune signatures and stool microbiome. Up to 78 patients will be enrolled under the assumption of an improved 12-month PFS from 50% (S) to 75% (E), using a two-sided α=0.1, power=80%, and accounting for loss-to-follow-up and stratification using IMDC criteria 1-2 vs 3-6. Clinical trial information: NCT04090710.

The treatment of metastatic kidney cancer is rapidly evolving with the shift from immune checkpoint inhibitor monotherapy to combination therapy. In 2018, the combination of nivolumab–ipilimumab received regulatory approval and multiple positive clinical trials were reported with combinations of PD-1 or PD-L1 inhibitors in conjunction with antiangiogenic drugs.

Between December 2005 and October 2009, FDA approved six targeted therapies shown to significantly extend survival for advanced renal cell carcinoma (RCC) patients in clinical trials. This study aimed to examine changes in survival between the pretargeted and targeted therapy periods in advanced RCC patients in a real‐world setting. Utilizing the 2000–2010 SEER Research files, a pre–post study design with a contemporaneous comparison group was employed to examine differences in survival outcomes for patients diagnosed with advanced RCC (study group) or advanced prostate cancer (comparison group, for whom no significant treatment innovations happened during this period) across the pretargeted therapy era (2000–2005) and the targeted therapy era (2006–2010). RCC patients diagnosed in the targeted therapy era (N = 6439) showed improved survival compared to those diagnosed in the pretargeted therapy era (N = 7231, hazard ratio (HR) for all‐cause death: 0.86, P

Resume Objectifs Evaluer les donnees recentes de la litterature concernant les indications therapeutiques dans les cancers du rein localement avances et/ou metastatiques et analyser le benefice des therapies ciblees depuis leur adjonction dans l’arsenal de traitement. Methode Nous avons effectue une revue de la litterature en utilisant les mots-cles suivants, Renal Cell Carcinoma, Target Therapy, Surgery, Metastases, RECIST sur le moteur de recherche Pubmed pour rechercher des articles indexes entre les annees 1999 et 2014. Nous avons retenu les donnees des grandes etudes cliniques des differentes therapies ciblees dont nous avons fait la synthese et rapportons les recommandations actuelles d’utilisation pratique dans les cancers du rein a cellules claires (CRCC) localement avances et/ou metastatiques (LA/M). Resultats Les essais randomises recents de grande taille ont demontre l’efficacite des differentes therapies ciblees dans la prise en charge des CRCC en termes de survie sans progression. Conclusion L’unification et pratiquement « mondialisation » des protocoles doit beaucoup aux propositions therapeutiques, issues des resultats des differentes essais prospectifs et basees sur un niveau d’evidence eleve.

mTORC1 inhibitors were first approved for the use in metastatic kidney cancer. However, observed treatment benefit was highly heterogeneous among patients. Through case-based cancer genomic sequencing of therapeutic outliers, we can begin to appreciate the convergent evolution of given cancer pathways/phenotypes beyond genes in kidney cancer, like a braided river. Clin Cancer Res; 22(10); 2320–2. ©2016 AACR. See related article by Kwiatkowski et al., p. 2445

A 63-year-old male with a past history of left nephrectomy due to clear cell renal cell carcinoma at the age of 57 was admitted for further evaluation. Enhanced abdominal computed tomography revealed that there were several hypervascular tumors in the pancreas and a single hypervascular tumor in the gallbladder. Laparoscopic cholecystectomy was performed to obtainpathological diagnosis. Microscopically, the tumor in the gallbladder was filled with clear cells and was diagnosed as metastatic gallbladder cancer from the previous clear cell renal cell carcinoma. Metastatic renal cell carcinoma to the gallbladder is extremely rare, with reported frequencies of less than0. 6% in687 autopsies. We hereinreport a case inwhich cholecystectomy enabled a successful diagnosis and review the reported 22 cases in Japanese patients.

La Presse Medicale - In Press.Proof corrected by the author Available online since vendredi 4 juillet 2014

Resume Le traitement du CRM chez les sujets âges est identique a celui des patients plus jeunes. Alors que les cytokines etaient classiquement contrindiquees chez les patients de plus de 70 ou 75 ans (notamment l’IL2), les nouvelles therapeutiques ciblees ont ete evaluees sans limitation d’âge et l’ensemble des etudes de phase III a inclus des patients de plus de 80 ans. Globalement, il ne semble pas y avoir de difference d’efficacite en fonction de l’âge (sauf peut-etre pour le temsirolimus). Concernant la tolerance, elle est satisfaisante avec l’ensemble des therapeutiques. La diminution de doses est un peu plus frequente, ce qui doit rendre prudent, notamment avec le sunitinib pour lequel une correlation directe entre la dose administree et l’efficacite a ete rapportee. Compte-tenu des donnees disponibles, aucune adaptation de dose en fonction de l’âge n’est recommandee dans le CRM.

Meeting abstracts An estimated 63,920 cases of kidney cancer will occur in the USA in 2015, and about 13,860 deaths will occur. The incidences of kidney cancer has steadily increased by 2-4% each year. Currently high dose IL (Interleukin)-2, VEGF (vascular endothelial growth factor) inhibitors, and

489 Background: The introduction of thyrosinkinase inhibitors (TKI) changed the treatment of metastatic kidney cancer fundamentally. To elaborate the potential impact of TKI therapies, we studied trends in OS for patients with primary metastatic kidney cancer between 1998 and 2014 in Austria. Methods: All patients with primary metastatic kidney cancer aged ≥18 years, diagnosed from 1998-2009 were derived from the ANCR (n=2134). Patients diagnosed from 2004-2006 (n=316) were excluded (transition period of systemic therapies). To evaluate differences in OS between patients treated in preTKI-era and TKI-era, two periods were defined: 1998-2003 (before the introduction of Sunitinib in Austria, P1; n=926) and 2006-2009 (P2; n=542). Follow-up was complete until December 31st, 2014. OS rates were estimated by using the Kaplan-Meier method. The Cox proportional hazard model was used to calculate hazard ratios (HR). Results: A total 1468 patients was included in the analysis. The median age of the study population was 70 yrs (sd ±12) and did not differ between the two eras. The incidence of T1 tumors increased from 6.6% in P1 to 10% in P2 while T4 tumors decreased from 15% to 6.5% (p

502 Background: With nine new targeted and immunotherapeutic agents for metastatic kidney cancer (mRCC) since 2005, there is no randomized data supporting sequencing cytoreductive nephrectomy (CN) and newer systemic therapies (ST). Increased disease control with ST engenders concern that CN may shorten life or delay therapy. Thus, in all the best prognostic candidates, initial ST as a “litmus” test may be advocated prior to CN. We evaluated use of CN after initial ST, hypothesizing receipt of deferred CN to be associated with increased survival time, markers of increased performance status, less rapid disease, and socioeconomic status. Methods: The National Cancer Database was screened for adult patients with biopsy-proven mRCC treated with initial systemic therapy between 2006-2013. Covariates included demographic, oncologic, hospital-level, and geographic variables. Unadjusted and multivariable logistic regression was performed, identifying factors associated with CN after initial ST. Results: Of 14,651 patients treated with initial ST for mRCC, 709 (4.8%, median OS 19 months, IQR 9-35) underwent delayed CN compared with 13,942 (95.2%, median OS 5 months, IQR 2-13) treated with ST alone. On multivariable analysis, survival ≥3 months was highly associated with receipt of CN (OR 10.6, 95% CI 5.5, 20.5). However, of 9,796 surviving ≥3 months, only 689 (7%) underwent CN. Factors associated with lower odds of CN included older age, greater comorbidity, higher clinical stage (T and N), and unfavorable metastatic sites (i.e., brain, bone, liver) with all p

Treatment of metastatic kidney cancer has changed dramatically in the past years with the use of VEGF-targeted therapies and mTOR inhibitors. However, resistance occurs. We report here two cases of patients who benefited, both on disease control and side effects, from the addition of bevacizumab to temsirolimus, after progression on the mTOR inhibitor alone.

Renal cell carcinoma (RCC) is a disease that can be effectively treated when localized within the kidney; ‘therapy’ often involves the surgical removal of the diseased organ and the surrounding tis...

624 Background: The risk of intravenous contrast induced nephropathy (CIN) is not well described in post-nephrectomy or metastatic kidney cancer. Patients with nephrectomies and tumors of the kidney frequently have CKD and often require serial contrast imaging placing them at risk for CIN. Methods: This is a retrospective review of 292 patients metastatic RCC and/or with partial or radical nephrectomies (PN or RN) for kidney tumors at Mayo Clinic Arizona or Florida from 2010 through 2014. Results: We found 207 patients received at least one contrast scan, of whom 99 had metastatic RCC, 104 had local RCC and 4 had oncocytoma. At baseline (pre-nephrectomy) 41% (46/113) and 15% (11/76) of RN and PN respectively had CKD stages 3-5 and with at least 3 months follow up after both nephrectomy and contrast exposure 61% (68/113) and 33% (25/76) RN and PN developed CKD stages 3-5 respectively. The median contrast exposure scans were 4 (range 1-30 scans) with a median follow up of 26 months (range 1-96 months). In all patients with at least one contrast exposure, the median change in creatinine and GFR from baseline was 0.2 mg/dL and 8 ml/min respectively. Excluding those with bilateral nephrectomy there were 8 (8/207 = 4%) CIN events, 6/113 had a radical nephrectomy and 2/76 with 1 partial nephrectomy and 1 aborted nephrectomy (P value 0.37). Of these patients 5 (5/99 = 5%) had metastatic RCC and 3 (3/104 = 3%) local RCC. The median contrast exposure scans for patients with CIN were 8 (range 3-12) and median follow up was 31 months (range 4-47 months). Three patients all with metastatic RCC developed acute kidney injury from CIN requiring dialysis and died of complications in part related to CIN during that hospital stay or soon after. Two other patients developed CKD stage III after CIN events and 3 patients (including the one with a partial nephrectomy) showed no significant change in GFR after CIN. Conclusions: In this retrospective analysis, CIN after nephrectomy or metastatic RCC contributed to acute renal failure with 3 deaths and 2 patients developing CKD stage III. Further analysis is required to determine what risk factors for CIN in this population.

Renal cell carcinoma is the most lethal urologic malignancy. Up to 30% of patients with kidney cancer have metastatic disease and 30% of those treatedfor local or locally advanced disease will progress to metastases. Radical nephrectomy is the standard treatment for the management of nondisseminated kidney cancer, but the role of cytoreductive nephrectomy for patients with metastatic disease is controversial. In this paper, the rationale for cytoreductivenephrectomy is described and the currently available evidence for andagainst it is evaluated. The different approaches to defining prognostic factorsto select which patients will benefit from cytoreductive nephrectomy willalso be described. Finally, the role of cytoreductive nephrectomy in the eraof new targeted therapies is discussed.

We evaluate presentation and outcome of patients with metastatic RCC to the gallbladder from our institution and published literature.Patients with a history of gallbladder metastasis from RCC were selected from our institution's prospective database. A systematic PubMed search was performed to identify articles describing patients with metastatic RCC to the gallbladder. The final cohort included 33 patients: 4 from our institution and 29 from 28 previously published cases. Survival analysis was conducted using log-rank Kaplan-Meier analysis.Median patient age was 63 years and the majority of patients were male. Most patients were asymptomatic and diagnosed with gallbladder metastasis on imaging performed for surveillance or staging. The median time to gallbladder metastasis following nephrectomy was 4 years. Metastasis to the gallbladder occurred both synchronously (33%) and metachronously (67%). Of the patients with available histology, all had clear cell RCC (n = 28). Of all patients, 13 (39%) had metastasis only to the gallbladder, while 20 (61%) had additional sites of metastasis. The most common sites of additional metastasis were contralateral kidney (30%), pancreas (21%), lung (18%), adrenal (18%), and lymph nodes (9%). All patients underwent cholecystectomy. At a median follow up time of 1.5 years after cholecystectomy, 54% of patients had no evidence of disease, 14% were alive with metastasis, 23% had died from metastatic RCC, and 9% died from causes unrelated to their cancer.Gallbladder metastasis from RCC is a rare event that may occur synchronously or metachronously with most patients being asymptomatic. Clear cell carcinoma appears to be the primary pathology associated with gallbladder metastasis. High rates of bilateral RCC and pancreatic metastasis suggest novel associations in patients with RCC and gallbladder metastasis.

Sorafenib is an oral Raf kinase inhibitor, approved for the treatment of advanced renal cancer. Clinical investigation of the safety and feasibility of sorafenib therapy in patients with impaired renal function was performed in this study.The protocol was approved by the Human Investigation Committee of Wayne State University. Medical records of patients with metastatic renal cancer at Wayne State University started on sorafenib between November 2005 to January 2007 were reviewed. Patients with a calculated creatinine clearance (CrCl) of 60 mL/min or less (chronic kidney disease stage 3 or greater per Kidney Disease Outcomes Quality Initiative guidelines) were deemed to have renal insufficiency.A total of 32 patients who met the selection criteria were analyzed. Fourteen of 32 (44%) patients had renal insufficiency (range, 32-60 mL/min). Median age was 71 years in patients with CrClor = 60 mL/min and 54 years in those with60 mL/min. Incidence of diarrhea (57% vs. 33%) and hand-foot syndrome (86% vs. 56%) were higher in the renal-dysfunction group. Dose interruptions and dose reductions were noted in 57% and 43% of patients with renal dysfunction versus 28% and 22% in those without. No significant differences were noted in response rate, progression-free survival or overall survival.Renal insufficiency is frequently observed in patients with advanced renal cancer. Sorafenib therapy can be safely delivered in patients with mild and moderate renal dysfunction, and efficacy appears to be maintained.

Background Recent data have shown that cardiotoxicity represents a potentially important side-effect in patients treated with sunitinib. We reviewed cardiac adverse events in patients with metastatic renal cell carcinoma (RCC) who underwent treatment with this agent. Patients and methods The medical records of 175 patients with metastatic RCC treated with sunitinib at eight Italian institutions were retrospectively reviewed. Alterations in left ventricular ejection fraction (LVEF) and blood pressure were evaluated. Patients with preexisting cardiac risk factors were specifically scrutinized for increased expression of cardiac changes. Results Grade 3 hypertension was seen in 17 patients (9.7%); in 12 of these 17, hypertension developed after receiving the third sunitinib cycle. Among these 17 patients, 12 (70.6%) also experienced left ventricular systolic (LVEF) dysfunction; in all, 33 of the 175 patients (18.9%) developed some degree of cardiac abnormality, of which 12 were classified as grade 3 LVEF dysfunction and/or congestive heart failure (CHF) (6.9%). Significant univariate associations for predictors of CHF were history of hypertension (P = 0.008), history of coronary heart disease (P = 0.0005) and prior treatment with an angiotensin-converting enzyme inhibitor (P = 0.04). Multivariate analysis suggested that a history of coronary artery disease [odds ratio (OR) 18, 95% confidence interval (CI) 4–160, P = 0.005] and hypertension (OR 3, 95% CI 1.5–80, P = 0.04) was the only significant independent predictors of CHF. Conclusions Patients undergoing sunitinib, especially those with a previous history of hypertension and coronary heart disease, are at increased risk for cardiovascular events and should be monitored for exacerbations of their hypertension and for evidence of LVEF dysfunction during treatment.

It is important for us as urologists to keep up to date with new drugs being introduced for treating metastatic renal cancer, particularly in the era of the multidisciplinary team approach to cancer therapy. Authors from Rome cover this topic in this month's issue. In other mini reviews in this section, the topics of ejaculatory disorders and cryosurgery are described. Both are relevant to modern management of common urological disorders. Finally there is an historical contribution. There is no such section for these manuscripts, but occasionally subjects of interest are presented which are intended to be of general educational value to the reader. I believe that the paper on prisons presented in this issue to be such a case.

Preclinical and early clinical data suggest that antiangiogenic treatments may lead to more aggressive tumors. In this issue of Cell Reports, Blagoev et al. (2013) show that sunitinib, a multikinase inhibitor with antiangiogenic effects, does not worsen the survival of patients with metastatic kidney cancer.

C. Gordon McCarty, 75, a retired Bayer research adviser and university relations manager and a member of the ACS Board of Directors from 2000 to 2008, died on June 20 at his home in Dataw Island, S.C. He died from complications of late-stage metastatic kidney cancer, which was diagnosed only seven weeks earlier. McCarty earned a B.S. degree magna cum laude in 1957 and an M.S. degree in 1959, both in chemistry at Wichita State University. He then earned a Ph.D. in organic chemistry at the University of Illinois, Urbana-Champaign, in 1963. McCarty began his career as an assistant professor of chemistry at West Virginia University, becoming a professor of chemistry there in 1977. He moved to Pittsburgh in 1980 to become an analytical laboratory coordinator at Bayer and was promoted to research adviser for the company in 1986. The following year, McCarty began serving as Bayer’s manager of university relations, helping the company ...